ABSTRACT
The broad spectrum of brain injuries in preterm newborns and the plasticity of the central nervous system prompts us to seek solutions for neurodegeneration to prevent the consequences of prematurity and perinatal problems. The study aimed to evaluate the safety and efficacy of the implantation of autologous bone marrow nucleated cells and bone marrow mesenchymal stem cells in different schemes in patients with hypoxic-ischemic encephalopathy and immunological encephalopathy. Fourteen patients received single implantation of bone marrow nucleated cells administered intrathecally and intravenously, followed by multiple rounds of bone marrow mesenchymal stem cells implanted intrathecally, and five patients were treated only with repeated rounds of bone marrow mesenchymal stem cells. Seizure outcomes improved in most cases, including fewer seizures and status epilepticus and reduced doses of antiepileptic drugs compared to the period before treatment. The neuropsychological improvement was more frequent in patients with hypoxic-ischemic encephalopathy than in the immunological encephalopathy group. Changes in emotional functioning occurred with similar frequency in both groups of patients. In the hypoxic-ischemic encephalopathy group, motor improvement was observed in all patients and the majority in the immunological encephalopathy group. The treatment had manageable toxicity, mainly mild to moderate early-onset adverse events. The treatment was generally safe in the 4-year follow-up period, and the effects of the therapy were maintained after its termination.
Subject(s)
Drug Resistant Epilepsy , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Male , Female , Drug Resistant Epilepsy/therapy , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Hypoxia-Ischemia, Brain/therapy , Hypoxia-Ischemia, Brain/pathology , Infant , Bone Marrow Cells/metabolism , Bone Marrow Cells/cytology , Child, Preschool , Child , Treatment OutcomeABSTRACT
Mutations in RAG1 gene may result in different types of severe combined immunodeficiencies. In this study, we compare clinical symptoms and laboratory findings in four children with identical mutation in RAG1 gene. All of analyzed patients presented symptoms of severe combined immunodeficiencies associated or not with Omenn syndrome (OS) features. In our patients two different types of variants in RAG1 gene were detected. The first of the mutation was the deletion of AA dinucleotide at position c.256_257 (p.Lys86ValfsTer33), the second gene variant was substitution c.2867T>C (p.Ile956Thr). In Patient 1 we detected that compound heterozygous mutations involved both of the mentioned variants. Whereas, in Patients 2, 3 and 4, we confirmed the presence of the dinucleotide deletion but in a homozygous state. In all described patients, sequence analysis of RAG2 gene did not reveal any nucleotide changes. Our data show that mutation c.256_257delAA in RAG1 gene seems to occur quite frequently in the polish patients with severe combined immunodeficiency and may result in classical OS as well as in severe combined immunodeficiency without clinical and laboratory features of OS when occurred in homozygous state. The same mutation but in heterozygous state, in combination with other mutation in RAG1 gene, may result in incomplete OS.
Subject(s)
Homeodomain Proteins/genetics , Mutation , Severe Combined Immunodeficiency/genetics , Case-Control Studies , Child , Child, Preschool , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Female , Gene Deletion , Genetic Variation , Heterozygote , Homozygote , Humans , Infant , Male , Mothers , Nuclear Proteins/genetics , Poland , Sequence Analysis, DNAABSTRACT
The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (p<0.1) while recipient age and donor-recipient gender relation were not significant. Moreover, CXCL12-3'-A-positive patients were less prone to early HHV-6 reactivation (2/34 vs. 19/69, p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome of unrelated HSCT.
Subject(s)
Chemokine CXCL12/genetics , Hematopoietic Stem Cell Transplantation , Polymorphism, Single Nucleotide , Unrelated Donors , Adolescent , Adult , Age Factors , Alleles , Child , Child, Preschool , Female , Genotype , Graft vs Host Disease/genetics , Herpesvirus 6, Human/physiology , Histocompatibility Testing , Humans , Infant , Male , Middle Aged , Sex Factors , Transplantation, Homologous , Virus Activation , Young AdultABSTRACT
OS is a variant of SCID characterized by generalized erythroderma, alopecia, eosinophilia, and elevated IgE levels. It is fatal unless treated with allogeneic HSCT, which is the only curative approach. However, treatment related complications and graft rejection are major obstacles to the success of treatment. In this report, we describe a patient with OS, complicated by prolonged cytomegalovirus infection, successfully treated by reduced intensity conditioning allogeneic HSCT from sibling donor.
